Prolonged exposure of rats to oxygen at pressures greater than 0.5 ata is associated with morphologic and biochemical changes, and subsequent death. The course of hyperoxia can be accelerated by hyperbaric pressure, dietary vitamin E or selenium deficiency, or by pretreatment with injected disulfiram. In contrast, increased survival in hyperoxia can be established by pre-exposure to 0.8 ata O2 or by pretreatment with endotoxin. Recently, in our laboratory, plasma fibronectin, a stable alpha-2glycoprotein, has been measured in rats exposed to one or four ata O2. In exposed rats there was a progressive elevation in serum Fn, significant at 48 hours of 1 ata O2, or at 105 min of 4 ata O2. This pattern is unique for this protein in injury states, and for plasma measurements in oxygen toxicity. The elevation occurs at a time when the injury is sublethal. The tissue source and the cellular mechanism for this elevation remain obscure, but the rise after a defined delay suggests enhanced protein synthesis. We propose to study the alteration of plasma fibronectin levels in models of altered sensitivity to oxygen, and to compare plasma fibronectin concentrations with those of acute phase reactants in control and oxygen exposed rats. We will correlate these changes with studies of endothelial amine clearance, prostaglandin dehydrogenase activity and respiratory burst of alveolar macrophages, which give in vitro insight into metabolic derangements which are progressive with oxygen exposure. We will seek to elucidate the metabolic mechanism for the elevation of plasma fibronectin levels, evaluating the balance among fragmentation of circulating fibronectin, enhanced synthesis and secretion, and depressed degradation. Finally, we will study the tissue source for plasma fibronectin in the isolated perfused organ with emphasis on the lung, liver, and systemic endothelium, which may provide important evidence for an early sytemic manifestation of oxygen exposure. A significant number of patients are treated yearly with increased oxygen concentations, but no satisfactory method exists at present to determine an early deleterious effect of oxygen. These studies give insight into mechanisms for pulmonary oxygen toxicity and the feasibility for investigating the clinical utility of plasma fibronectin determination.